Opportunistic infections associated with AIDS pose very serious problems because of their exceedingly high morbidity and mortality. For their part, Mycobacterium avium and M. intracellulare, two organisms belonging to M. avium complex (MAC), are the most often isolated bacteria from AIDS patients. Although in recent years, some progress has been made, by and large, there is no viable drug and /or combinations of drugs effective against MAC, especially in AIDS patients. Conventional therapies with multiple drug combinations involving isoniazid, rifampin, ethambutol, streptomycin, ethionamide, and cycloserine are still widely used, as well as prophylactic treatment with rifabutin. The use of clofazimine and ciprofloxacin has also been reported. Studies on new quinolones (sparfloxacin, difloxacin, WIN 57273), macrolides, folate antagonists and antimcobacterial anitbiotics are being actively pursued along with novel strategies involving drugs inhibiting mycobacterial cell wall biosynthesis. The role of various cytokines in enhancing host immune defenses against MAC infections is also discussed.